Antimicrobial inserts for medical devices

ABSTRACT

Inserts can be formed with elution characteristics to cause the inserts to elute an antimicrobial agent when subject to a fluid within a medical device. An insert can be formed with a desired geometry to allow the insert to be compression fit within a medical device to prevent the insert from moving or becoming dislodged once inserted into the medical device. The material may also be hygroscopic so that the insert swells when subject to a fluid thereby enhancing the compression fit of the device within the medical device. In some cases, the material can be reinforced using an internal structure. Inserts can be formed in many ways including by casting, thermoforming, or extrusion. In some cases, the inserts can be formed using a peel-away sleeve or material. The peel-away sleeves can be formed of a non-sticky material which facilitates removal of the inserts once the inserts have cured.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/606,833, filed Jan. 27, 2015, and titled ANTIMICROBIAL INSERTS FORMEDICAL DEVICES, which is a continuation-in-part of U.S. patentapplication Ser. No. 14/185,831, filed Feb. 20, 2014 and titledANTIMICROBIAL INSERTS FOR MEDICAL DEVICES, which is incorporated hereinin its entirety.

BACKGROUND OF THE INVENTION

The present invention relates generally to inserts for medical devicesthat are configured to elute an antimicrobial agent. The inserts of thepresent invention can be particularly beneficial when used within one ormore components of an infusion system.

Catheters are commonly used for a variety of infusion therapies. Forexample, catheters are used for infusing fluids, such as normal salinesolution, various medicaments, and total parenteral nutrition into apatient, withdrawing blood from a patient, as well as monitoring variousparameters of the patient's vascular system.

Catheter-related bloodstream infections are caused by the colonizationof microorganisms in patients with intravascular catheters and I.V.access devices. These infections are an important cause of illness andexcess medical costs. More importantly, these infections often result inpatient deaths.

Many techniques have been employed to reduce the risk of infection froma catheter or other intravenous device. For example, catheters have beendesigned that employ an antimicrobial lubricant or an antimicrobialcoating on an inner or outer surface of the catheter. Similarly,antimicrobial lubricants or coatings have been applied to the surfacesof other components of a catheter assembly, components attached to thecatheter assembly, or other medical devices which may come in directcontact with the patient's vasculature or in contact with a fluid thatmay enter the patient's vasculature. Further, some devices or componentsare made of a material that is impregnated with an antimicrobial agent.

Although these techniques have been beneficial, there are variousdrawbacks that limit their usefulness. For example, it can be difficultand/or expensive to apply an antimicrobial coating or lubricant to thecomplex internal and external geometries of many devices or components.Also, some devices or components are preferably made of a material thatis not suitable for the application of an antimicrobial coating or thatcannot be impregnated with an antimicrobial agent. Because of suchdifficulties, the current techniques for providing antimicrobialprotection are oftentimes not used or, if used, are not adequatelyapplied to provide maximum antimicrobial protection.

BRIEF SUMMARY OF THE INVENTION

The present invention extends to inserts for medical devices. Theinserts are manufactured of a material that includes an antimicrobialagent and that has elution characteristics so that the antimicrobialagent is eluted from the material at a desired rate to provideantimicrobial protection to a medical device in which the insert iscontained. An insert can be formed with a desired geometry to allow theinsert to be compression fit within a medical device to prevent theinsert from moving or becoming dislodged once inserted into the medicaldevice. The material may also be hygroscopic so that the insert swellswhen subject to a fluid thereby enhancing the compression fit of thedevice within the medical device. In some cases, the material can bereinforced using an internal structure and/or an adhesive.

The inserts of the present invention can be used within a variety ofmedical devices to provide a desired level of antimicrobial protectionto the medical devices. An insert can be designed to have a surface areathat is sufficient for the volume of the location in which the insert iscontained so that a sufficient amount of antimicrobial agent is elutedto disinfect the fluid within the area within a desired amount of time.Examples of medical devices or components in which the inserts of thepresent invention can be used include ports, stop cocks, male luers,female luers, IV sets, needleless connectors, respirators, catheters,devices for fluid infusion to the body or aspiration from the body,surgical instruments etc.

The inserts of the present invention can be manufactured in variousways. For example, the inserts can be formed in a desired geometry bycasting, thermoforming, or extrusion. In some cases, the inserts can beformed using a peel-away sleeve. The peel-away sleeves can be formed ofa non-sticky material which facilitates removal of the inserts once theinserts have cured.

In one embodiment, the present invention is implemented as an inset fora medical device. The insert comprises a base material having elutioncharacteristics, and an antimicrobial agent contained within the basematerial so that the antimicrobial agent is eluted from the basematerial when the base material is exposed to or comes in contact with afluid.

In some embodiments, the base material comprises a hygroscopic materialthat swells upon absorbing a fluid.

In some embodiments, the insert is bonded to a surface of the medicaldevice using a curable adhesive.

In some embodiments, the insert is mechanically fastened to the medicaldevice using features such as threads, snap-fits etc.

In some embodiments, the insert is made of a hydrophilic material tofacilitate elution of a water soluble antimicrobial agent where the basematerial comprises a hydrophilic polymer such as urethane acrylate or apolyurethane polymer.

In some embodiments, the antimicrobial agent comprises between 0.1% and40% w/w of the insert.

In some embodiments, the insert is formed by curing the base materialcontaining the antimicrobial agent in a desired form. In someembodiments, the form comprises a tube shape or a rod shape. In someembodiments, the tube shape has an outer diameter that is equal to orlarger than an inner diameter of a lumen of a medical device withinwhich the insert will be placed.

In some embodiments, the insert is placed within a catheter adapterhaving a septum, wherein the insert secures the septum in place.

In some embodiments, the insert is formed within a peel-away sleeve. Insome embodiments, the peel-away sleeve comprises one of: polyolefin;fluoropolymer; polyvinyl chloride; or ethylene vinyl acetate. In someembodiments, the insert is formed within a mold that is lined with oneor more peel-away sheets.

In some embodiments, the insert comprises a reinforcing substructurecontained within the base material.

In another embodiment, the present invention is implemented as a medicaldevice comprising an insert that elutes an antimicrobial agent. Theinsert comprises a base material having elution characteristics, and anantimicrobial agent contained within the base material so that theantimicrobial agent is eluted from the base material when the basematerial is exposed to a fluid.

In some embodiments, the insert comprises a lumen through which fluidpasses within the medical device.

In some embodiments, the insert attaches to and extends from a firstmedical device such that the insert is configured to contact and/or beinserted within a second medical device when the two medical devices areconnected. As such, the eluted antimicrobial agent from the insertprovides antimicrobial protection to both of the medical devices.

In another embodiment, the present invention is implemented as a methodfor forming an insert for a medical device. A base material havingelution characteristics is combined with an antimicrobial agent to forma base material matrix. The base material matrix is then formed into aninsert that is sized and shaped to be inserted and contained within amedical device.

In some embodiments, the base material matrix is formed into the insertusing UV curing, heat curing, or heat forming.

In some embodiments, the insert contains materials that at leastpartially dissolve into the fluid resulting in partial or even completedissolution of the insert upon use.

In some embodiments, they insert comprises a matrix, such as across-linked polymer or a ceramic, that does not dissolve in to thefluid while the antimicrobial agent contained within the matrix at leastpartially dissolves.

In some embodiments, forming the base material matrix into the insertcomprises placing the base material matrix within a peel-away material.

In some embodiments, the method includes placing the insert within themedical device such that the insert is exposed to a fluid to cause theantimicrobial agent to elute from the insert into the fluid.

In some embodiments, the insert may serve a mechanical function such asa support feature for other components of the medical device or a fluidconduit or a mating feature to another device or component.

Some implementations of the present invention further provideantimicrobial luer stoppers. Antimicrobial strips and antimicrobialannular inserts are also provided for various medical devices, such asfor insertion within a side port of a catheter adapter. Variousembodiments of the present invention further include a medical devicehaving an antimicrobial side port that is coupled to the medical devicevia an adhesive and/or a weld.

Some implementations of the instant invention further provide a methodfor forming an antimicrobial insert within the interior of a medicaldevice via an injection molding process. The method utilizes a medicaldevice having an injection port formed in a sidewall of the medicaldevice, wherein the injection port is in fluid communication with anon-tapered, interior surface of the device. The antimicrobial materialis injected into the medical device after inserting a tapered mandrelinto the interior of the medical device, wherein the antimicrobialmaterial is injected into a wedge-shaped gap formed between the outersurface of the mandrel and the non-tapered, interior surface of thedevice.

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter.

Additional features and advantages of the invention will be set forth inthe description which follows, and in part will be obvious from thedescription, or may be learned by the practice of the invention. Thefeatures and advantages of the invention may be realized and obtained bymeans of the instruments and combinations particularly pointed out inthe appended claims. These and other features of the present inventionwill become more fully apparent from the following description andappended claims, or may be learned by the practice of the invention asset forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to describe the manner in which the above-recited and otheradvantages and features of the invention can be obtained, a moreparticular description of the invention briefly described above will berendered by reference to specific embodiments thereof which areillustrated in the appended drawings. Understanding that these drawingsdepict only typical embodiments of the invention and are not thereforeto be considered to be limiting of its scope, the invention will bedescribed and explained with additional specificity and detail throughthe use of the accompanying drawings in which:

FIGS. 1A-1H each illustrate an insert in accordance with one or moreembodiments of the invention. FIGS. 1A and 1B illustrate perspectiveviews of inserts having tube shapes in accordance with representativeembodiments of the present invention. FIG. 1C illustrates a top view ofan insert having a tube shape with an irregular internal surface inaccordance with a representative embodiment of the present invention.FIG. 1D illustrates a cross-sectional view of a tube-shaped insert thatincludes an expanded opening on one end in accordance with arepresentative embodiment of the present invention. FIGS. 1E and 1Fillustrate inserts that include a reinforcing substructure in accordancewith representative embodiments of the present invention. FIGS. 1G and1H illustrate inserts that have a rod shape in accordance withrepresentative embodiments of the present invention.

FIGS. 2A-2E illustrate examples of medical devices in which insertsconfigured in accordance with one or more embodiments of the inventioncan be placed. FIGS. 2A-2C illustrate a catheter adapter that includesone or more inserts in various positions in accordance with arepresentative embodiment of the present invention. FIG. 2D illustratesa ported intravenous catheter that includes inserts in accordance with arepresentative embodiment of the present invention. FIG. 2E illustratesa cap that includes a rod-shaped insert in accordance with arepresentative embodiment of the present invention.

FIGS. 3A and 3B illustrate how an insert can be used to retain a septumin place within a catheter adapter in accordance with a representativeembodiment of the present invention. FIG. 3A illustrates a prior artcatheter adapter that employs a bump formed in the internal wall of thecatheter adapter to hold the septum in place in accordance with arepresentative embodiment of the present invention. FIG. 3B illustrateshow an insert can be used in place of a bump to retain the septum inaccordance with a representative embodiment of the present invention.

FIGS. 4A-4C illustrate how an insert can be formed using a peel-awaysleeve in accordance with various representative embodiments of thepresent invention. FIG. 4A illustrates a peel-away sleeve prior to thesleeve being filled with a base material matrix in accordance with arepresentative embodiment of the present invention. FIG. 4B illustratesthe peel-away sleeve after the sleeve has been filled with the basematerial matrix in accordance with a representative embodiment of thepresent invention. FIG. 4C illustrates the peel-away sleeve being peeledoff of the insert after the base material matrix has been cured to formthe insert in accordance with a representative embodiment of the presentinvention.

FIG. 5A illustrates a top view of a peel-away sleeve having an irregularinternal surface in accordance with a representative embodiment of thepresent invention. FIG. 5B illustrates a top view of an insert that canbe formed using the peel-away sleeve of FIG. 5A in accordance with arepresentative embodiment of the present invention.

FIG. 5C illustrates a cross-sectional view of a mold that is lined witha peel-away material in accordance with a representative embodiment ofthe present invention. FIG. 5D illustrates a cross-sectional view of aninsert that can be formed using the mold of FIG. 5C in accordance with arepresentative embodiment of the present invention.

FIG. 6 illustrates a cross-sectional view of a stopcock medicalconnector having a female luer fitting in which is seated anantimicrobial luer stopper in accordance with a representativeembodiment of the present invention.

FIG. 7A illustrates a perspective view of an antimicrobial luer stopperin accordance with representative embodiments of the present invention.FIG. 7B illustrates a perspective view of the antimicrobial luer stopperin accordance with representative embodiments of the present invention.

FIG. 8A illustrates a cross-sectional view of a catheter adapter havinga side port with interior grooves comprising an antimicrobial materialin accordance with a representative embodiment of the present invention.FIG. 8B illustrates a top plan view of the catheter adapter having theside port with interior grooves comprising the antimicrobial material inaccordance with a representative embodiment of the present invention.

FIG. 9 illustrates a cross-sectional side view of a catheter adaptercomprising an antimicrobial side port that has been welded into thecatheter adapter in accordance with a representative embodiment of thepresent invention.

FIG. 10 illustrates a cross-sectional side view of a catheter adaptercomprising a side port having an inner, annular recess into which isinserted an antimicrobial insert in accordance with a representativeembodiment of the present invention.

FIG. 11A illustrates a cross-sectional side view of a female luer porthaving at least one injection port for receiving an antimicrobialmaterial, further demonstrating a method for injecting the antimicrobialmaterial to form an antimicrobial coating on an inner surface of thefemale luer port in accordance with a representative embodiment of thepresent invention. FIG. 11B illustrates a cross-sectional side view ofthe female luer port having at least one injection port for receivingthe antimicrobial material, further demonstrating the method forinjecting the antimicrobial material to form the antimicrobial coatingon the inner surface of the female luer port in accordance with arepresentative embodiment of the present invention. FIG. 11C illustratesa cross-sectional side view of the female luer port having at least oneinjection port for receiving the antimicrobial material, furtherdemonstrating the method for injecting the antimicrobial material toform the antimicrobial coating on the inner surface of the female luerport in accordance with a representative embodiment of the presentinvention. FIG. 11D illustrates a cross-sectional side view of thefemale luer port having at least one injection port for receiving theantimicrobial material, further demonstrating the method for injectingthe antimicrobial material to form the antimicrobial coating on theinner surface of the female luer port in accordance with arepresentative embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention extends to inserts for medical devices. Theinserts are manufactured of a material that includes an antimicrobialagent and that has elution characteristics so that the antimicrobialagent is eluted from the material at a desired rate to provideantimicrobial protection to a medical device in which the insert iscontained. An insert can be formed with a desired geometry to allow theinsert to be compression fit within a medical device to prevent theinsert from moving or becoming dislodged once inserted into the medicaldevice. The material may also be hygroscopic so that the insert swellswhen subject to a fluid thereby enhancing the compression fit of thedevice within the medical device. In some cases, the material can bereinforced using an internal structure and/or an adhesive.

The inserts of the present invention can be used within a variety ofmedical devices to provide a desired level of antimicrobial protectionto the medical devices. An insert can be designed to have a surface areathat is sufficient for the volume of the location in which the insert iscontained so that a sufficient amount of antimicrobial agent is elutedto disinfect the fluid within the area within a desired amount of time.Examples of medical devices or components in which the inserts of thepresent invention can be used include ports, stop cocks, male luers,female luers, IV sets, needleless connectors, respirators, catheters,devices for fluid infusion to the body or aspiration from the body,surgical instruments etc.

The inserts of the present invention can be manufactured in variousways. For example, the inserts can be formed in a desired geometry bycasting, thermoforming, or extrusion. In some cases, the inserts can beformed using a peel-away sleeve. The peel-away sleeves can be formed ofa non-sticky material which facilitates removal of the inserts once theinserts have cured.

In one embodiment, the present invention is implemented as an inset fora medical device. The insert comprises a base material having elutioncharacteristics, and an antimicrobial agent contained within the basematerial so that the antimicrobial agent is eluted from the basematerial when the base material is exposed to or comes in contact with afluid.

In some embodiments, the base material comprises a hygroscopic materialthat swells upon absorbing a fluid.

In some embodiments, the insert is bonded to a surface of the medicaldevice using a curable adhesive.

In some embodiments, the insert is mechanically fastened to the medicaldevice using features such as threads, snap-fits etc.

In some embodiments, the insert is made of a hydrophilic material tofacilitate elution of a water soluble antimicrobial agent where the basematerial comprises a hydrophilic polymer such as urethane acrylate or apolyurethane polymer.

In some embodiments, the antimicrobial agent comprises between 0.1% and40% w/w of the insert.

In some embodiments, the insert is formed by curing the base materialcontaining the antimicrobial agent in a desired form. In someembodiments, the form comprises a tube shape or a rod shape. In someembodiments, the tube shape has an outer diameter that is equal to orlarger than an inner diameter of a lumen of a medical device withinwhich the insert will be placed.

In some embodiments, the insert is placed within a catheter adapterhaving a septum, wherein the insert secures the septum in place.

In some embodiments, the insert is formed within a peel-away sleeve. Insome embodiments, the peel-away sleeve comprises one of: polyolefin;fluoropolymer; polyvinyl chloride; or ethylene vinyl acetate. In someembodiments, the insert is formed within a mold that is lined with oneor more peel-away sheets.

In some embodiments, the insert comprises a reinforcing substructurecontained within the base material.

In another embodiment, the present invention is implemented as a medicaldevice comprising an insert that elutes an antimicrobial agent. Theinsert comprises a base material having elution characteristics, and anantimicrobial agent contained within the base material so that theantimicrobial agent is eluted from the base material when the basematerial is exposed to a fluid.

In some embodiments, the insert comprises a lumen through which fluidpasses within the medical device.

In some embodiments, the insert attaches to and extends from a firstmedical device such that the insert is configured to contact and/or beinserted within a second medical device when the two medical devices areconnected. As such, the eluted antimicrobial agent from the insertprovides antimicrobial protection to both of the medical devices.

In another embodiment, the present invention is implemented as a methodfor forming an insert for a medical device. A base material havingelution characteristics is combined with an antimicrobial agent to forma base material matrix. The base material matrix is then formed into aninsert that is sized and shaped to be inserted and contained within amedical device.

In some embodiments, the base material matrix is formed into the insertusing UV curing, heat curing, or heat forming.

In some embodiments, the insert contains materials that at leastpartially dissolve into the fluid resulting in partial or even completedissolution of the insert upon use

In some embodiments, they insert comprises a matrix, such as across-linked polymer or a ceramic, that does not dissolve in to thefluid while the antimicrobial agent contained within the matrix at leastpartially dissolves.

In some embodiments, forming the base material matrix into the insertcomprises placing the base material matrix within a peel-away material.

In some embodiments, the method includes placing the insert within themedical device such that the insert is exposed to a fluid to cause theantimicrobial agent to elute from the insert into the fluid.

In some embodiments, the insert may serve a mechanical function such asa support feature for other components of the medical device or a fluidconduit or a mating feature to another device or component.

Antimicrobial inserts in accordance with one or more embodiments of theinvention can be comprised of a base material matrix and one or moreantimicrobial agents. In some embodiments, the base material matrix canbe a UV curable, hydrophilic material that contains an antimicrobialagent with controlled release (elution) characteristics. Alternatively,a base material can be coated with an antimicrobial coating from whichan antimicrobial agent will elute when subject to a fluid. Examples ofmaterials that could be used to form the antimicrobial inserts of thepresent invention includes those disclosed in U.S. Pat. No. 8,512,294titled Vascular Access Device Antimicrobial Materials And Solutions;U.S. patent application Ser. No. 12/397,760 titled AntimicrobialCompositions; U.S. patent application Ser. No. 12/476,997 titledAntimicrobial Coating Compositions; U.S. patent application Ser. No.12/490,235 titled Systems And Methods For Applying An AntimicrobialCoating To A Medical Device; and U.S. patent application Ser. No.12/831,880 titled Antimicrobial Coating For Dermally Invasive Devices.Each of these patent documents is incorporated herein by reference.

In one particular embodiment, the antimicrobial agent used to form aninsert can be chlorhexidine including chlorhexidine diacetate (CHA) andchlorhexidine gluconate (CHG). However, any other antimicrobial agentthat will elute from a base material or from a coating on a basematerial could be used.

Inserts may be formed using any suitable technique including in-moldcuring, UV cured profile extrusion, cutting, sheet stamping, etc. Aprimary benefit of employing inserts to provide antimicrobial protectionwithin medical devices is that the inserts can be formed in a separateprocess from the process used to form the medical devices. For example,unlike prior art approaches which apply an antimicrobial coating withinthe lumen of a catheter adapter or other medical device, the inserts ofthe present invention can be formed independently from the catheteradapter or other medical device and then inserted. In this way, theinserts can be manufactured much more easily and inexpensively whencompared to prior art approaches.

Similarly, because the inserts are independent of the medical device inwhich the inserts will be used, antimicrobial protection can be moreeasily provided in a greater variety of devices. For example, somedevices are made of a material that is not suited for antimicrobialcoatings (e.g. an antimicrobial coating may not stick to the material).The inserts of the present invention, however, can be used within amedical device made of virtually any material to provide antimicrobialprotection within the medical device.

In some embodiments, the base material used for an insert can behygroscopic so that the base material will swell once contacted by afluid, such as saline or blood. The swelling of the insert can increasethe compression fit within the medical device to prevent the insert frommoving or becoming dislodged during use. In this way, the use of insertsis further facilitated because no additional structure or securingmechanism (e.g. an adhesive or structural feature) may be required toretain the insert at the desired position within the medical device. Asa result, medical devices can be provided with antimicrobial protectionwith greater ease and at a reduced cost. Of course, the inserts of thepresent invention could be used with a securing structure or mechanismif desired.

In some embodiments, the inserts can be partially cured prior toinsertion in a medical device and then fully cured once within themedical device. In other embodiments, the inserts can be fully curedprior to being inserted.

In some embodiments, it may be desirable to increase the strength orrigidity of an insert. In such cases, the insert can include areinforcing substructure that is contained within the base material.Examples of suitable reinforcing substructures include metals, plastics,fibers, etc. For example, when an insert is formed as a tube, atube-shaped reinforcing structure can be contained within the basematerial.

The shape and size of an insert can be configured so that the rate ofelution of the antimicrobial agent is sufficient to provide a desiredlevel of antimicrobial protection. The rate of elution of theantimicrobial agent is dependent on the surface area of the insert thatis exposed to the fluid. Accordingly, various shapes and sizes ofinserts can be employed to obtain the necessary surface area to providethe desired amount of antimicrobial protection. In some embodiments, theratio of the insert's exposed surface area to fluid volume (i.e. thevolume of fluid to be treated by the antimicrobial agent within theinsert) is between 0.1 cm²/ml and 50 cm²/ml.

In some embodiments, an insert may be contained within or separated fromthe fluid volume by a hydrophilic filter membrane. A hydrophilic filtermembrane can be used to further control the elution characteristics ofthe base material (e.g. by controlling the flow of fluid along thesurface area of the insert) and can also prevent any particles thatbreak off from the insert from passing into the fluid stream. An exampleof a material suitable for use as a hydrophilic filter includespolyethersulfone (PES).

Any material having elution characteristics can be employed as the basematerial of an insert. Examples of suitable materials include UV curedacrylate-urethanes and heat-cured polymers which soften in water, suchas hygroscopic polyurethanes. These materials can be preferred overmaterials that do not soften in water because they enhance thecompression fit of the inserts when they are wet.

The amount of antimicrobial agent used within the matrix can be variedto provide a desired mechanical property or elution characteristic. Forexample, in some instances a matrix is provided which comprises solidantimicrobial agent particles in an amount representing approximately0.1-40% w/w of the matrix. These particles may range in size from 100 nm(fine powder) to 0.15 mm (salt-sized crystals). Additional additives mayalso be used to attain a particular characteristic. These additionaladditives include: multiple antimicrobial agents to widen the spectrumof microbes that will be affected; viscosity modifiers such as silica;color modifiers such as dyes or titanium dioxide; strength or stiffnessmodifiers such as glass fibers, ceramic particles such as zirconia, ormetallic fibers; radiopacity modifiers such as barium sulfate; andmagnetic susceptibility enhancers such as gadolinium chelates.

Inserts in accordance with the present invention can be formed invarious shapes and sizes and can be used in various types of medicaldevices and for various functions. Examples of the different types ofinserts that are encompassed within the present invention are providedin the figures and will be described below.

Referring to FIGS. 1A-1H, antimicrobial inserts according to embodimentsof the invention can be formed in various shapes and sizes as necessaryfor use in a particular medical device. For example, FIGS. 1A and 1Billustrate examples of tube-shaped inserts 101 and 102 respectively.Inserts 101 and 102 can be formed to have an outer diameter that isapproximately the same as or slightly larger than the inside diameter ofa lumen of a medical device. In this way, inserts 101 and 102 can becompression fit within the lumen of the medical device to impartantimicrobial protection within the lumen.

In some embodiments, inserts 101 and 102 can be designed only to form achannel through which a fluid within the lumen of the medical deviceflows. As the fluid contacts and flows through inserts 101 and 102, anantimicrobial agent contained within the material of the inserts 101 and102 is eluted into the fluid thereby killing any microbes that may bepresent within the fluid. In such cases, the inner diameter of inserts101 and 102 can be configured so as to not significantly restrict fluidflow through the lumen or to provide a desired flow characteristicthrough the lumen.

In other embodiments, the inner diameters of inserts 101 and 102 areconfigured to conform to the outer diameter of another device which isinserted into the lumens of inserts 101 and 102. In such cases, inserts101 and 102 are placed so that the inserted device contacts theantimicrobial agent contained within the material of inserts 101 and 102thereby killing any microbes which may be present on the outer surfacesof the inserted device.

In some embodiments, the inner surface of a tube-shaped insert can havea varying or irregular diameter to increase the surface area that isexposed to a fluid. FIG. 1C illustrates an example of a tube-shapedinsert 103 that has an inner surface with a varying diameter. The ridgesand channels formed within the inner surface effectively increase thesurface area of insert 103 that is exposed to a fluid.

In addition to tube-shaped inserts that have a generally circularopening, inserts having other external and internal shapes can beformed. For example, some inserts can have an internal opening or lumenthat is in the shape of a plus sign, a star, a square, etc. Also, someinserts can have an outer surface that has a triangular, square, orrectangular cross-section. Accordingly, inserts can be formed in anydesired shape and/or size to fit within an intended medical device.

FIG. 1D illustrates an example of an insert 104 having an expandedopening on one end. The expanded opening can facilitate use of insert104 with another device. For example, insert 104 could be placed withinthe lumen of a port or a female luer so that, when another device (e.g.a male luer) is inserted into the port or female luer, the other devicemay insert into the expanded opening.

FIGS. 1E and 1F illustrate examples of inserts 105 and 106 that includea reinforcing substructure 120. The reinforcing substructure 120 canextend the full length of the insert as is shown in FIG. 1E or onlyalong a portion of the length as is shown in FIG. 1F. In the examplesshown in FIGS. 1E and 1F, the reinforcing substructure 120 comprises atube shape to conform to the tube shape of inserts 105 and 106. However,a reinforcing substructure can have other shapes that do not conform tothe shape of the insert as long as the reinforcing substructure can becontained within the material of the insert. Also, in some embodiments,more than one reinforcing substructure can be employed within an insert.For example, two or more rings of reinforcing substructure could beemployed within a tube-shaped insert. In some embodiments, thereinforcing substructure can be comprised of fibers that are mixed withthe base material to form a reinforced composite base material.

With reference again to inserts 105 and 106, reinforcing material 120can serve to enhance the compression fit of inserts 105 and 106 withinthe lumen of a medical device. For example, reinforcing material 120,which is in the shape of a tube, can have an outer diameter that isslightly less than the inside diameter of the lumen in which the insertwill be placed. Accordingly, once the inserts are inserted into thelumen, the inside wall of the lumen and the outside surface of thereinforcing material will compress the base material of the inserts tosecurely hold the inserts in place.

FIGS. 1G and 1H illustrate additional examples of inserts 107 and 108.In contrast to inserts 101-106, inserts 107 and 108 are formed in a rodshape. Such rod-shaped inserts can be used in various ways includingwithin a cap or device that is inserted into the lumen of anotherdevice. As described above, reinforcing material can be used to increasethe rigidity of inserts 107 and 108 and to prevent inserts 107 and 108from breaking. Although not shown, rod-shaped inserts can be formed thathave non-circular cross-sections. For example, the cross-sectional shapeof a rod can be star-shaped to increase the surface area of the insert.

FIGS. 2A-2E illustrate examples of various devices in which inserts canbe used to provide antimicrobial protection within the devices. FIGS.2A-2C illustrate various locations within a catheter adapter 200 wherean insert may be placed. In FIGS. 2A and 2B, a single insert 201 and 202respectively is placed within the lumen of catheter adapter 200. In FIG.2C, two inserts 203 and 204 are placed within the lumen of catheteradapter 200. As shown, inserts 201-204 have different shapes and sizesdepending on the intended purpose of the insert.

FIG. 2D illustrates an example where a ported intravenous catheter(PIVC) 210 includes three inserts 211, 212, and 213. The size and shapeof each insert 211, 212, and 213 can be designed to impart the desiredantimicrobial protection to the location of the insert. For example,insert 213 can be configured with a surface area and/or an elution rateso that an adequate amount of antimicrobial agent is eluted into fluidbeing injected through the port of the PIVC.

In each of the embodiments shown in FIGS. 2A-2D, the inserts can bemanufactured independently of the catheter adapters and then insertedinto the catheter adapters after manufacturing. Because inserts can bemanufactured at minimal cost and can be easily added to the catheteradapter by insertion, there is little additional cost for producingcatheter adapters that provide antimicrobial protection. This is incontrast to the substantial additional cost required to add anantimicrobial coating or lubricant on the inner surfaces of catheteradapters as is the case with prior art approaches.

FIG. 2E illustrates an example where a cap 220 includes a rod-shapedinsert 221. Cap 220 may be configured to attach to a port, female luer,or other opening of a medical device. In such cases, insert 221 can beconfigured to insert into the port, female luer, or other opening wherethe insert will be exposed to fluid. The elution of an antimicrobialagent from insert 221 can provide antimicrobial protection to the port,female luer, or other opening of the device. Because insert 221 can bemanufactured independently of cap 220, caps which provide antimicrobialprotection can be manufactured more easily and cheaply than with currenttechniques.

In some embodiments, the inserts of the present invention can performfunctions in addition to providing antimicrobial protection. FIGS. 3Aand 3B illustrate one example of how an insert can perform additionalfunctions. FIG. 3A illustrates a common prior art catheter adapter 300that employs a septum 301 for controlling the flow of blood within thecatheter adapter. Septum 301 is designed to form a seal around anintroducer needle that passes through the septum and to remain sealedwhen the introducer needle is removed from the catheter adapter anduntil another device is inserted through the septum.

To ensure that septum 301 remains in place while the introducer needleis withdrawn and when other devices are inserted through the septum, theinner surface of catheter adapter 300 includes a bump 302. Although bump302 is effective in retaining septum 301 in place, the use of bump 302can increase the cost of manufacturing catheter adapter 300 or may makeit difficult to apply an antimicrobial coating within catheter adapter300.

As shown in FIG. 3B, bump 302 can be replaced by an insert 311 whichholds septum 301 in place. In other words, by placing insert 311adjacent to septum 301, insert 311 can hold septum 301 in place. As aresult, catheter adapter 310 can be designed without bump 302.Additionally, as described above, insert 311 can provide antimicrobialprotection within the lumen of catheter adapter 310.

As described above, insert 311 can be configured to form a tightcompression fit within catheter adapter 310. This compression fit can beenhanced in some embodiments by employing a hygroscopic base material sothat insert 311 will swell when subject to a fluid. Similarly, one ormore reinforcing substructures can be employed as desired to give insert311 the necessary strength or structural rigidity to hold septum 301 inplace.

Alternatively, insert 311 can be comprised of a material that may notinclude elution characteristics (i.e. that does not elute anantimicrobial agent). In such cases, an antimicrobial coating can beapplied to insert 311 to provide the desired antimicrobial protectionwithin the lumen of catheter adapter 310. In such embodiments, insert311 can provide the benefit of allowing a material suitable for aparticular antimicrobial coating to be used to hold septum 301 in place.Examples of suitable materials include polycarbonate and co-polyester.In contrast, in prior art catheter adapter designs, the material (ofwhich bump 302 was made) typically was not ideal for the application ofan antimicrobial coating. By employing insert 311, catheter adapter 310can be made of any desired material (whether or not the material issuitable for the application of an antimicrobial coating) because theantimicrobial protection is provided by insert 311.

Whether insert 311 is comprised of a material that elutes anantimicrobial agent or that is coated with an antimicrobial agent, theinsert provides both functions of securing septum 301 in place anddisinfecting the lumen of catheter adapter 310. In this way, themanufacture of catheter adapters that include antimicrobial protectioncan be facilitated.

The inserts of the present invention can be made in many different waysincluding by pouring or injecting an unpolymerized formulation into anopen mold for UV curing or into an injection mold for heat curing. Also,some inserts can be formed using extrusion or coextrusion over asubstrate material. Similarly, some inserts can be formed usingthermoplastics such as polyurethane which may be shaped using heatstamping.

One particular example of how inserts can be formed is shown in FIGS.4A-4C. These figures illustrate the use of a peel-away sleeve as a moldfor forming inserts having a rod shape. FIG. 4A illustrates a peel-awaysleeve 400 prior to being filled with an uncured base matrix. Peel-awaysleeve 400 can be made of a material that has a low peel strength sothat, once the matrix has been cured, the sleeve can be easily peeledaway. The low peel strength of the sleeves ensures that the inserts willhave a smooth exterior surface. The use of sleeves also minimizes theoccurrence of flash on the inserts.

For example, for inserts that are made of an acrylate-based or acyanoacrylate-based material, the sleeve can be made of polyolefin,fluoropolymer, polyvinyl chloride, or ethylene vinyl acetate. Examplesof suitable polyolefin include polyethylene (low density, liner lowdensity, high density, ultra-high molecular weight polyethylene, andderivatives thereof) and polypropylene (polypropylene homopolymer,polypropylene copolymer, and derivatives thereof). Examples of suitablefluoropolymer include polytetrafluoroethylene, fluorinatedethylene-propylene, polyvinylidene fluoride,polyethylenetetrafluoroethylene, and derivatives thereof.

Sleeve 400 can be formed in any suitable manner including by extrusion,molding, of thermoforming. Once formed, sleeve 400 can be filled withthe base matrix 401 (e.g. CHA or CHG mixed in acrylate adhesive) as isshown in FIG. 4B. The base matrix is then cured using, for example, UVlight, LED light, heat, etc. The sleeve 400 is then easily peeled awayfrom the cured matrix 401 as shown in FIG. 4C leaving the insertmaterial which may be cut to size as necessary.

Sleeves of various shapes and sizes can be used to form a tube of adesired shape or size. For example, FIG. 5A illustrates a sleeve 500with a varied internal diameter that can be used to form an insert 501having a cross-sectional shape of increased surface area.

In some embodiments, rather than filling the sleeve with the base matrix(i.e. rather than using the sleeve as the mold), a sheet made of asimilar material as sleeve 400 can be used as a liner of a cast ormolding tool. For example, FIGS. 5C and 5D illustrate a cross-sectionalview of peel-away sheets 510 and 511 that are used as liners for a mold520. A base matrix can be poured into mold 520 between sheets 510 and511 and then cured. Once cured, the cured matrix contained within thesheets 510 and 511 can be removed from mold 520. Sheets 510 and 511 canthen be easily peeled from the cured matrix leaving an insert 530 asshown in FIG. 5D. Insert 530 is an example of an insert that can beplaced within a port to provide antimicrobial protection to fluidcontained within the port. Similarly techniques can be employed to forma tube-shaped insert such as those shown in FIGS. 1A-1F or inserts ofother shapes.

Referring now to FIG. 6, some embodiments of the present inventionfurther include an antimicrobial insert comprising a luer stopper 610that is fitted within a female luer fitting 602 of a medical device 600,such as a stopcock medical connector. Luer stopper 610 are generallyconfigured or designed to contact the front or distal end of a male luerdevice upon insertion into a female luer fitting 602. Luer stopper 610may prevent over-insertion of a male luer device. Luer stopper 610 mayfurther provide correct alignment of the male luer device within fitting602.

In some instances, luer stopper 610 comprises a polymer material havingantimicrobial properties. In some instances, luer stopper 610 comprisesan antimicrobial coating material that is applied to the outer surfaceof luer stopper 610. For example, in some embodiments an antimicrobialcoating is applied to the flange surface 612, shown in FIGS. 6 and 7A.In some embodiments, an antimicrobial coating is applied to one or moresurfaces that are in direct contact with a fluid that is present withina fluid pathway 620 through medical device 600. Following an infusionprocedure, any stagnant fluid remaining in luer fitting 602 is in fluidcommunication or contact with the antimicrobial luer stopper 610, or anantimicrobial coating applied thereon, whereby an antimicrobial agentwithin the stopper or coating material is eluted into the stagnant fluidto prevent the growth and/or colonization of microbes. In someinstances, luer stopper 610 prevents the infusion of live microbes, aswell as prevents the growth of biofilm within the device 600.

Some embodiments of luer stopper 610 further comprise one or more tabs630, as shown in FIGS. 6 and 7B. Tabs 630 are generally provided toassist in accurately positioning a luer connector within female luerfitting 602. In some instances, tabs 630 are provided to achieve aproper insertion depth of a luer connector, and to ease removal of theluer connector from fitting 602. In some instances, tabs 630 furthercomprise an antimicrobial coating material, wherein the thickness of thecoating material does not interfere with the actuation or removal of themale luer connector.

The number and size of tabs 630, as well as the concentration of theantimicrobial agent within the antimicrobial coating may be varied tooptimize microbial kill efficacy with regards to elution rate andduration. In some instances, tabs 630 are formed in a continuous ring orluer stopper having a top surface and or side surfaces that are coatedfor maximal microbial effects or kill duration. For example, in someembodiments to top or flange surface 612 comprises a surface area of0.001 in². In other embodiments, luer stopper 610 comprises an interiorsurface area 640 from 0.012 in² to 0.02 in², wherein the luer stopper610 is molded to extend into a port portion of the medical device 600,as shown. Further, in some embodiments luer stopper 610 comprises 2, 3,4, 5, 6, or more tabs 630. The addition of tabs 630 may increase thesurface area of luer stopper 610, thereby providing for additionalsurface area that may be coated with an antimicrobial coating. Thus,both the antimicrobial concentration and surface area can be optimizedto achieve the targeted kill rate and duration.

The flange surface 612, tabs 630, and interior surface 640 may be coatedwith an antimicrobial coating according to any known method. In someembodiments, the aforementioned surfaces may be coated via a pad printmethod. In other embodiments, the aforementioned surfaces may be coatedby simply dispensing antimicrobial coating drops onto the desiredsurfaces. The coating material is then cured using UV light, LED light,or heat. As many IV access components are transparent or translucent, afast UV/LED light cure can be achieved for high productivity.

Referring now to FIGS. 8A and 8B, some embodiments of the presentinvention further include an antimicrobial insert comprising strips 810that are applied to the inner surface 822 of a side port 802 of amedical device 800, such as a catheter adapter. Strips 810 may comprisean antimicrobial, polymer material having an antimicrobial agent that isconfigured to elute out of the polymer material when contacted by afluid. In some embodiments, strips 810 are coated with an antimicrobialcoating, wherein an antimicrobial agent within the antimicrobial coatingis configured to elute out of the antimicrobial coating when exposed toor contacted by a fluid.

In some embodiments, inner surface 822 comprises recessed channels 824having a width, depth, and length configured to receive strips 810.Strips 810 may be retained within channels 824 via any suitable method,for example, such as by an adhesive or plastic welding. In someembodiments, strips 810 are formed within channels 824 via an injectionmolding process whereby a mandrel is first fitted into side port 802 toprovide a gap between the outer surface of the mandrel and channels 824.Antimicrobial material is then injected into channels 824. The insertedmandrel retains the injected antimicrobial material within channels 824until the antimicrobial material is cured, such as by UV radiation. Themandrel is then removed from side port 802. In some instances, the outersurface of the mandrel is coating with non-stick or releasing materialprior to insertion within side port 802, thereby preventing adhesionbetween strips 810 and the outer surface of the mandrel.

In some embodiments, medical device 800 comprises an antimicrobial sideport 920, as shown in FIG. 9. Antimicrobial side port 920 generallyincludes a polymer material comprising an antimicrobial agent configuredto elute out of the polymer material when exposed to a fluid. In someinstances, medical device 800 comprises an opening 880 having a diameterthat is configured to receive antimicrobial side port 920. Side port 920is permanently secured within opening 880 via one or more known methods,for example, such as by an adhesive or plastic welding.

In some instances, side port 820 of medical device 800 comprises aninner, annular recess 890 having a circumference configured tocompatible receive an antimicrobial insert 1000, as shown in FIG. 10. Insome instances, annular recess 890 further comprises heat stakes 894that extend over a proximal end of antimicrobial insert 1000 to retaininert 1000 within side port 820.

Antimicrobial insert 1000 may comprise a polymer material having anantimicrobial agent configured to elute out of the polymer material whenexposed to a fluid. Alternatively, antimicrobial insert 1000 maycomprise a polymer material having an antimicrobial coating comprisingan antimicrobial agent, wherein the antimicrobial agent is configured toelute out of the coating material when exposed to a fluid. Further, insome embodiments antimicrobial insert 1000 comprises a polymer materialhaving an antimicrobial agent interspersed therein, and furthercomprises an antimicrobial coating having an antimicrobial agentdispersed therein, wherein the antimicrobial agents are configured toelute out of their respective carriers when exposed to a fluid.

Referring now to FIGS. 11A-11D, a method for forming an antimicrobialinsert 1110 within a female luer connector 1102 is shown. Someembodiments of the present invention provide a female luer connector1102 having a partially tapered inner surface 1120, wherein the proximalinterior surface 1122 of inner surface 1120 is tapered, and the distalinterior surface 1124 comprises parallel inner wall surfaces, i.e. notaper. Alternatively, distal interior surface 1124 may comprise areduced taper. Distal interior surface 1124 further comprises aninjection port 1130 having an outer opening 1132 and an inner opening1134, wherein outer opening 1132 is in fluid communication with theinterior of distal end 1124 via inner opening 1134. In some embodiments,distal interior surface 1124 further comprises a venting port 1140, asshown and discussed in connection with FIG. 11C.

Antimicrobial insert 1110 is formed within distal interior surface 1124by injecting an antimicrobial material 1170 into the interior of luerconnector 1102 via injection port 1130. Prior to injection ofantimicrobial material 1170, a mandrel 1180 is inserted within theinterior of female luer connector 1102. Mandrel 1180 comprises a taperedouter surface 1182 having an taper angle θ that is equal to the taperangle θ of proximal interior surface 1122, commonly referred to as the“luer taper”.

Mandrel 1180 is inserted into the interior of luer connector 1102 untilthe distal end 1184 of mandrel 1180 contacts the distal end surface 1126of luer connector 1102, as shown in FIG. 11B. In some embodiments, thelength 1140 of distal interior surface 1124, and the angle of luer tapere are selected so that outer surface 1182 fully contacts proximalinterior surface 1122 when distal end 1184 contacts distal end surface1126. Distal end surface 1126 and distal end 1184 are further configuredto have mating surfaces, thereby forming a sealed interface when the twosurfaces are in contact. Luer taper e of proximal interior surface 1122and outer surface 1182 further form a sealed interface when the twosurfaces are in contact.

When mandrel 1180 is fully inserted within luer connector 1102, awedge-shaped gap is formed between outer surface 1182 of mandrel 1180and the parallel wall surfaces of distal interior surface 1124, as shownin FIG. 11C. Antimicrobial insert 1110 is formed within the wedge-shapedgap as antimicrobial material 1170 is injected therein via injectionport 1130, such as by a syringe 1190. Alternatively, injection port 1130may be accessed via automated injection machinery.

In some embodiments, luer connector 1102 further comprises a ventingport 1140 that is positioned within distal interior surface 1124,approximately opposite injection port 1130. Venting port 1140 providesfor the release of air and excess antimicrobial material 1170 fromdistal interior surface 1124 (i.e. the wedge-shaped gap) during theinjection process. In some embodiments, luer connector 1102 comprises aplurality of injection ports. Luer connector 1102 may further comprise aplurality of venting ports.

Mandrel 1180 remains positioned within luer connector 1102 untilantimicrobial material 1170 is cured. In some instances, a releasing ornon-stick agent is applied to outer surface 1182 prior to insertion ofmandrel 1180 within luer connector 1102. The releasing agent is providedto prevent adhesion between the cured antimicrobial material 1170 andouter surface 1182. Once cured, mandrel 1170 is removed from luerconnector 1102 and antimicrobial insert 1110 remains within distalinterior surface 1124, as shown in FIG. 11D.

The method described above may alternatively be used to apply anantimicrobial material onto the outer surface of an internal (i.e. male)fluid fitting. For example, antimicrobial material may be injectedthrough a hole on the inner surface of the fluid fitting to fill arecess or gap on the outer surface of the fluid fitting. Prior to theinjection of the antimicrobial material, the fitting would be seatedinto tooling to control the shape of the injected antimicrobialmaterial.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

The invention claimed is:
 1. A method for forming an insert within amedical device, the method comprising: providing a medical device havinga partially tapered inner surface, wherein a distal portion of thepartially tapered inner surface comprises interior walls that areparallel; inserting a tapered mandrel into an interior of the medicaldevice, the tapered mandrel having a luer taper that is approximatelyequal to a luer taper of a tapered portion of the partially taperedinner surface, an outer surface of the tapered mandrel forming a sealedinterface with the tapered portion of the partially tapered innersurface, a distal end of the tapered mandrel forming a sealed interfacewith a distal end surface of the distal portion of the partially taperedinner surface, wherein a wedge-shaped gap is provided between the outersurface of the tapered mandrel and the parallel interior walls of thepartially tapered inner surface; injecting an antimicrobial materialinto the wedge-shaped gap; curing the antimicrobial material; and removethe tapered mandrel.
 2. The method of claim 1, wherein the base materialmatrix is cured using one of: UV curing, heat curing, or heat forming.3. The method of claim 1, further comprising a step for providing aninjection port though a wall surface of the medical device, wherein theinjection port is in fluid communication with the wedge-shaped gap. 4.The method of claim 1, further comprising: coating the outer surface ofthe tapered mandrel with a releasing agent prior to inserting thetapered mandrel within the interior of the medical device.